Scholars@Duke
James William Wisler

James William Wisler

Assistant Professor of Medicine
Medicine, Cardiology
jim.wisler@duke.edu
3320 Wake Forest Rd, Suite 200, Raleigh, NC 27609
3320 Wake Forest Rd, Suite 200, Raleigh, NC 27609
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Selected Publications

The β-arrestin-biased β-adrenergic receptor blocker carvedilol enhances skeletal muscle contractility.

Journal Article Proc Natl Acad Sci U S A · June 2, 2020 A decrease in skeletal muscle strength and functional exercise capacity due to aging, frailty, and muscle wasting poses major unmet clinical needs. These conditions are associated with numerous adverse clinical outcomes including falls, fractures, and incr ... Full text Open Access Link to item Cite

β-arrestin 1 regulates β2-adrenergic receptor-mediated skeletal muscle hypertrophy and contractility.

Journal Article Skelet Muscle · December 27, 2018 BACKGROUND: β2-adrenergic receptors (β2ARs) are the target of catecholamines and play fundamental roles in cardiovascular, pulmonary, and skeletal muscle physiology. An important action of β2AR stimulation on skeletal muscle is anabolic growth, which has l ... Full text Open Access Link to item Cite

β-Arrestin2 mediates progression of murine primary myelofibrosis.

Journal Article JCI Insight · December 21, 2017 Primary myelofibrosis is a myeloproliferative neoplasm associated with significant morbidity and mortality, for which effective therapies are lacking. β-Arrestins are multifunctional adaptor proteins involved in developmental signaling pathways. One isofor ... Full text Link to item Cite

Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor.

Journal Article Nat Chem Biol · September 2016 G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However ... Full text Link to item Cite

The role of β-arrestin2-dependent signaling in thoracic aortic aneurysm formation in a murine model of Marfan syndrome.

Journal Article Am J Physiol Heart Circ Physiol · November 2015 Ang II type 1a receptor (AT1aR)-mediated activation of MAPKs contributes to thoracic aortic aneurysm (TAA) development in Marfan syndrome (MFS). β-Arrestin2 (βarr2) is known to mediate AT1aR-dependent MAPK activation, as well as proproliferative and profib ... Full text Link to item Cite

Antithrombotic therapy: new areas to understand efficacy and bleeding.

Journal Article Expert Opin Ther Targets · December 2014 INTRODUCTION: Therapeutic options for antithrombotic therapy are limited due to associated adverse bleeding events. Traditionally, the antithrombotic effects of these agents have been closely linked with concomitant risks in bleeding complications. AREAS C ... Full text Link to item Cite

Recent developments in biased agonism.

Journal Article Curr Opin Cell Biol · April 2014 The classic paradigm of G protein-coupled receptor (GPCR) activation was based on the understanding that agonist binding to a receptor induces or stabilizes a conformational change to an 'active' conformation. In the past decade, however, it has been appre ... Full text Link to item Cite

Emerging paradigms in arterial thrombosis.

Journal Article J Thromb Thrombolysis · January 2014 A traditional perspective of arterial thrombosis begins with vessel wall injury and exposure of subendothelial proteins, including collagen and tissue factor, to circulating cellular and non-cellular components. Adhesion and activation of platelets, mediat ... Full text Link to item Cite

Targeting β-arrestin2 Enhances Survival in a Murine Model of Chronic Myeloid Leukemia

Conference Blood · November 15, 2013 AbstractBackgroundChronic myeloid leukemia (CML) is a myeloproliferative neoplasm of hematopoietic stem cells characterized by presenc ... Full text Cite

MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors.

Journal Article J Cell Biol · November 26, 2012 Lysosomal degradation of ubiquitinated β(2)-adrenergic receptors (β(2)ARs) serves as a major mechanism of long-term desensitization in response to prolonged agonist stimulation. Surprisingly, the βAR antagonist carvedilol also induced ubiquitination and ly ... Full text Link to item Cite

Challenges and opportunities in implementing pharmacogenomics testing in the clinics.

Journal Article Per Med · August 2012 The field of pharmacogenomics aims to incorporate individual patient genomic information into treatment selection. This is a rapidly evolving field with significant clinical promise. Implementation into clinical practice has several challenges that must be ... Full text Link to item Cite

A guidance pathway for the selection of novel anticoagulants in the treatment of atrial fibrillation.

Journal Article Crit Pathw Cardiol · June 2012 Oral anticoagulation with vitamin K antagonists has served as the primary treatment for the prevention of stroke and systemic embolization in patients with atrial fibrillation (AF) for decades. Over the past several years, multiple novel oral anticoagulant ... Full text Link to item Cite

Evaluation of dose requirements for prolonged bivalirudin administration in patients with renal insufficiency and suspected heparin-induced thrombocytopenia.

Journal Article J Thromb Thrombolysis · April 2012 Bivalirudin, a direct thrombin inhibitor, is indicated for patients with suspected heparin-induced thrombocytopenia (HIT) with anticipated percutaneous coronary intervention (PCI). Data is limited on dose selection among patients with renal insufficiency, ... Full text Link to item Cite

Oral factor Xa inhibitors for the long-term management of ACS.

Journal Article Nat Rev Cardiol · February 21, 2012 Despite considerable reductions in cardiovascular events in patients with an acute coronary syndrome (ACS) receiving dual antiplatelet therapy (DAPT), substantial residual risk persists. This unmet need has stimulated the development of anticoagulant drugs ... Full text Link to item Cite

Clinical trials update: Recent and ongoing studies in anticoagulation for atrial fibrillation

Journal Article Open Access Journal of Clinical Trials · January 1, 2012 Atrial fibrillation is the most common sustained cardiac arrhythmia in the adult population, with a marked increased risk associated with age. Perhaps the most devastating complications of atrial fibrillation include acute ischemic stroke or systemic embol ... Full text Cite

The β-arrestin-biased β-adrenergic receptor blocker carvedilol enhances skeletal muscle contractility.

Journal Article Proc Natl Acad Sci U S A · June 2, 2020 A decrease in skeletal muscle strength and functional exercise capacity due to aging, frailty, and muscle wasting poses major unmet clinical needs. These conditions are associated with numerous adverse clinical outcomes including falls, fractures, and incr ... Full text Open Access Link to item Cite

β-arrestin 1 regulates β2-adrenergic receptor-mediated skeletal muscle hypertrophy and contractility.

Journal Article Skelet Muscle · December 27, 2018 BACKGROUND: β2-adrenergic receptors (β2ARs) are the target of catecholamines and play fundamental roles in cardiovascular, pulmonary, and skeletal muscle physiology. An important action of β2AR stimulation on skeletal muscle is anabolic growth, which has l ... Full text Open Access Link to item Cite

β-Arrestin2 mediates progression of murine primary myelofibrosis.

Journal Article JCI Insight · December 21, 2017 Primary myelofibrosis is a myeloproliferative neoplasm associated with significant morbidity and mortality, for which effective therapies are lacking. β-Arrestins are multifunctional adaptor proteins involved in developmental signaling pathways. One isofor ... Full text Link to item Cite

Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor.

Journal Article Nat Chem Biol · September 2016 G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However ... Full text Link to item Cite

The role of β-arrestin2-dependent signaling in thoracic aortic aneurysm formation in a murine model of Marfan syndrome.

Journal Article Am J Physiol Heart Circ Physiol · November 2015 Ang II type 1a receptor (AT1aR)-mediated activation of MAPKs contributes to thoracic aortic aneurysm (TAA) development in Marfan syndrome (MFS). β-Arrestin2 (βarr2) is known to mediate AT1aR-dependent MAPK activation, as well as proproliferative and profib ... Full text Link to item Cite

Antithrombotic therapy: new areas to understand efficacy and bleeding.

Journal Article Expert Opin Ther Targets · December 2014 INTRODUCTION: Therapeutic options for antithrombotic therapy are limited due to associated adverse bleeding events. Traditionally, the antithrombotic effects of these agents have been closely linked with concomitant risks in bleeding complications. AREAS C ... Full text Link to item Cite

Recent developments in biased agonism.

Journal Article Curr Opin Cell Biol · April 2014 The classic paradigm of G protein-coupled receptor (GPCR) activation was based on the understanding that agonist binding to a receptor induces or stabilizes a conformational change to an 'active' conformation. In the past decade, however, it has been appre ... Full text Link to item Cite

Emerging paradigms in arterial thrombosis.

Journal Article J Thromb Thrombolysis · January 2014 A traditional perspective of arterial thrombosis begins with vessel wall injury and exposure of subendothelial proteins, including collagen and tissue factor, to circulating cellular and non-cellular components. Adhesion and activation of platelets, mediat ... Full text Link to item Cite

Targeting β-arrestin2 Enhances Survival in a Murine Model of Chronic Myeloid Leukemia

Conference Blood · November 15, 2013 AbstractBackgroundChronic myeloid leukemia (CML) is a myeloproliferative neoplasm of hematopoietic stem cells characterized by presenc ... Full text Cite

MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors.

Journal Article J Cell Biol · November 26, 2012 Lysosomal degradation of ubiquitinated β(2)-adrenergic receptors (β(2)ARs) serves as a major mechanism of long-term desensitization in response to prolonged agonist stimulation. Surprisingly, the βAR antagonist carvedilol also induced ubiquitination and ly ... Full text Link to item Cite

Challenges and opportunities in implementing pharmacogenomics testing in the clinics.

Journal Article Per Med · August 2012 The field of pharmacogenomics aims to incorporate individual patient genomic information into treatment selection. This is a rapidly evolving field with significant clinical promise. Implementation into clinical practice has several challenges that must be ... Full text Link to item Cite

A guidance pathway for the selection of novel anticoagulants in the treatment of atrial fibrillation.

Journal Article Crit Pathw Cardiol · June 2012 Oral anticoagulation with vitamin K antagonists has served as the primary treatment for the prevention of stroke and systemic embolization in patients with atrial fibrillation (AF) for decades. Over the past several years, multiple novel oral anticoagulant ... Full text Link to item Cite

Evaluation of dose requirements for prolonged bivalirudin administration in patients with renal insufficiency and suspected heparin-induced thrombocytopenia.

Journal Article J Thromb Thrombolysis · April 2012 Bivalirudin, a direct thrombin inhibitor, is indicated for patients with suspected heparin-induced thrombocytopenia (HIT) with anticipated percutaneous coronary intervention (PCI). Data is limited on dose selection among patients with renal insufficiency, ... Full text Link to item Cite

Oral factor Xa inhibitors for the long-term management of ACS.

Journal Article Nat Rev Cardiol · February 21, 2012 Despite considerable reductions in cardiovascular events in patients with an acute coronary syndrome (ACS) receiving dual antiplatelet therapy (DAPT), substantial residual risk persists. This unmet need has stimulated the development of anticoagulant drugs ... Full text Link to item Cite

Clinical trials update: Recent and ongoing studies in anticoagulation for atrial fibrillation

Journal Article Open Access Journal of Clinical Trials · January 1, 2012 Atrial fibrillation is the most common sustained cardiac arrhythmia in the adult population, with a marked increased risk associated with age. Perhaps the most devastating complications of atrial fibrillation include acute ischemic stroke or systemic embol ... Full text Cite

The diversity of wound presentation associated with freon contact frostbite injury.

Journal Article J Burn Care Res · 2010 The authors report two cases of patients presenting with chemical frostbite-like injuries to the hands and wrists after contact exposure to Freon liquid. Although the history and initial physical presentations were quite similar, the severity of these inju ... Full text Link to item Cite

beta-arrestin-biased agonism at the beta2-adrenergic receptor.

Journal Article J Biol Chem · February 29, 2008 Classically, the beta 2-adrenergic receptor (beta 2AR) and other members of the seven-transmembrane receptor (7TMR) superfamily activate G protein-dependent signaling pathways in response to ligand stimulus. It has recently been discovered, however, that a ... Full text Link to item Cite

A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling.

Journal Article Proc Natl Acad Sci U S A · October 16, 2007 For many years, beta-adrenergic receptor antagonists (beta-blockers or betaAR antagonists) have provided significant morbidity and mortality benefits in patients who have sustained acute myocardial infarction. More recently, beta-adrenergic receptor antago ... Full text Link to item Cite

Domain structure and DNA binding regions of beta protein from bacteriophage lambda.

Journal Article J Biol Chem · September 1, 2006 beta protein from bacteriophage lambda promotes a single-strand annealing reaction that is central to Red-mediated recombination at double-strand DNA breaks and chromosomal ends. beta protein binds most tightly to an intermediate of annealing formed by the ... Full text Link to item Cite

Probing the DNA sequence specificity of Escherichia coli RECA protein.

Journal Article Nucleic Acids Res · 2006 Escherichia coli RecA protein catalyzes the central DNA strand-exchange step of homologous recombination, which is essential for the repair of double-stranded DNA breaks. In this reaction, RecA first polymerizes on single-stranded DNA (ssDNA) to form a rig ... Full text Link to item Cite